Pestiviruses, including bovine viral diarrhea virus (BVD virus, or BVDV), have been isolated from several species of animals, both domestic and wild. Identified hosts for BVDV include buffalo, antelope, reindeer and various deer species, while unique pestivirus species have been identified in giraffes and pronghorn antelope. BVDV is a small RNA virus of the family Flaviviridae. It is closely related to other pestiviruses which are the causative agents of border disease in sheep and classical swine fever in pigs.
Disease caused by BVDV particularly in cattle is widespread, and can be economically devastating. BVDV infection in cattle can result in breeding problems, and can cause abortions or premature births. BVDV is capable of crossing the placenta of pregnant cattle, and may result in the birth of persistently infected (PI) calves that are immunotolerant to the virus and persistently viremic for the rest of their lives. Infected cattle can also exhibit “mucosal disease”, characterized by elevated temperature, diarrhea, coughing and ulcerations of the alimentary mucosa. These persistently infected animals provide a source for dissemination of virus within a herd and for further outbreaks of mucosal disease, and are highly predisposed to infection with microorganisms responsible for causing enteric diseases or pneumonia.
Among the BVDV vaccines currently available are those which contain chemically-inactivated wild-type virus, or those which contain modified-live (ML) BVDV. BVDV can be attenuated by repeated passage in bovine or porcine cells, or by chemically-induced mutations that confer a temperature-sensitive phenotype on the virus. However, existing inactivated and ML vaccines do not allow for the differentiation between vaccinated and naturally-infected animals.
A “marked” vaccine that could either contain an additional antigenic determinant which is not present in wild-type virus, or lack an antigenic determinant which is present in wild-type virus could be an effective tool for controlling BVDV infection in the field. US Patent Application 2010/0360055 (Luo et al., herein incorporated by reference in its entirety) describes the latter, a vaccine based upon a chimeric pestivirus vaccine in which the Erns protein of the BVDV is replaced with the Erns protein from a pronghorn pestivirus. This chimeric pestivirus was deposited as UC 25548 with ATCC®, and given the ATCC® deposit designation of PTA-9939. Accompanied by an appropriate diagnostic assay, use of this chimeric pestivirus would allow for the differentiation between animals to which it was administered, versus animals infected with wild-type BVDV or immunized with a conventional BVDV vaccine.